Smith‐Magenis syndrome: Clinical and behavioral characteristics in a large retrospective cohort

Abstract

Smith‐Magenis syndrome (SMS), characterized by dysmorphic features, neurodevelopmental disorder, and sleep disturbance, is due to an interstitial deletion of chromosome 17p11.2 (90%) or to point mutations in the RAI1 gene. In this retrospective cohort, we studied the clinical, cognitive, and behavioral profile of 47 European patients with SMS caused by a 17p11.2 deletion. We update the clinical and neurobehavioral profile of SMS. Intrauterine growth was normal in most patients. Prenatal anomalies were reported in 15%. 60% of our patients older than 10 years were overweight. Prevalence of heart defects (6.5% tetralogy of Fallot, 6.5% pulmonary stenosis), ophthalmological problems (89%), scoliosis (43%), or deafness (32%) were consistent with previous reports. Epilepsy was uncommon (2%). We identified a high prevalence of obstipation (45%). All patients had learning difficulties and developmental delay, but ID range was wide and 10% of patients had IQ in the normal range. Behavioral problems included temper tantrums and other difficult behaviors (84%) and night‐time awakenings (86%). Optimal care of SMS children is multidisciplinary and requires important parental involvement. In our series, half of patients were able to follow adapted schooling, but 70% of parents had to adapt their working time, illustrating the medical, social, educative, and familial impact of having a child with SMS.

Smith-Magenis Syndrome—Clinical Review, Biological Background and Related Disorders

“…Hands and feet are broad, short, and associated with brachydactyly ( Figure 1 C,D). Clinodactyly of the fifth fingers, 2–3 toe syndactyly, single transverse palmar crease, and finger pads may also be present; polydactyly has been reported twice [ 2 , 21 , 22 , 23 , 24 , 25 ]. Common dermatological features comprise xerosis, folliculitis of the back, acral pachydermia, and plantar keratoderma [ 12 ].…”

“…At birth, auxological parameters usually fall within the normal range [ 2 , 15 , 25 ]. The evolution of weight tends to be biphasic: in the first years of life, feeding difficulties may even cause failure to thrive whereas, from preadolescence onwards, overeating, low daily activity, and possible iatrogenic side effects often cause a significant ponderal gain [ 2 , 3 , 15 , 25 , 26 ]. From the age of 9 years, about half (47.8%) of individuals have a weight > 95th percentile [ 27 ].…”

“…Most of available data concerning height derive from series enriched in individuals in their middle/late childhood, so that the high prevalence of short stature (range 66% [ 28 ]–81% [ 3 ]) might not reflect the final height, which should place in the low percentiles of the normal range [ 29 ]. Moreover, a recent retrospective study found short stature to be less frequent than previously thought (25%) [ 25 ]. When addressing adults with SMS, short stature is reported to be present in 5–10% of them [ 15 ].…”

“…The total secretion of GH has been proved to be normal, although the peak values were lower than those of controls [ 30 ]. On the other hand, a GH deficit was identified three times [ 25 , 31 , 32 ] and replacement therapy might have proved to be effective for the final stature only once [ 32 ], requiring further studies to elucidate its real benefit. Microcephaly is not common and varies from 16% [ 25 ] to 37.5% [ 33 ].…”

Genomic Aberrations Associated with the Pathophysiological Mechanisms of Neurodevelopmental Disorders

“…In fact, it is known that neurodevelopmental disorders, such as autism and attention deficit hyperactivity disorder, occur when the regions responsible for classical chromosomal microdeletion syndrome are duplicated ( Table 1 ). Smith-Magenis syndrome is caused by the deletion of the 17p11 region [ 9 ], whereas, reciprocal duplication of this region causes Potocki-Lupski syndrome (MIM #610883), and the patients present with relatively severe developmental disorders [ 10 ]. The RAI1 gene, located on 17p11, is considered to be responsible for the neurodevelopmental disability in both Smith-Magenis and Potocki-Lupski syndromes [ 11 ].…”